Research Groups

Portrait Min Ae Lee-Kirsch

Min Ae Lee-Kirsch

Molecular genetics of autoimmune diseases

Previous and Current Research

Our group focuses on the molecular mechanisms that underlie autoimmunity. Systemic lupus erythematosus is a prototypic autoimmune disease with a broad spectrum of clinical manifestations. It is characterized by loss of tolerance to nuclear antigens such as nucleic acids, formation of auto-antibodies and immune complexes that deposit in tissues and cause widespread inflammation. There is strong evidence for a central role of type I-interferons (IFN) in lupus pathogenesis. Type I-IFNs play a pivotal role in the first line of defense against viral infections. Type I-IFNs sensitize cells to apoptosis, enhance dendritic cell activation, and promote activation and differentiation of auto-reactive B cells. If inappropriately activated, type I-IFNs drive a positive feed-back loop that leads to breakdown of tolerance.

Mutations in intracellular nucleic acid degrading enzymes such as TREX1 cause lupus or lupus-associated syndromes. Nuclease deficiency is thought to result in the intracellular accumulation of nucleic acid species, which induce an antiviral type I-IFN response by triggering intracellular innate sensors. Combining genetics, cell biology, mass spectrometry and fluorescence imaging techniques our studies aim to dissect the pathogenic pathways that lead to the phenotypic expression of autoimmune disease.

Future Projects and Goals
  • To identify genes causing monogenic and multifactorial autoimmune diseases in humans and to unravel their contribution to disease pathogenesis.
  • To understand the role of nucleic acid metabolism in mechanisms of immune defense and tolerance.
  • To translate basic science knowledge into clinically relevant concepts.
Methodological and Technical Expertise
  • molecular and cell biology
  • protein biochemistry/recombinant protein expression
  • confocal microscopy
  • flow cytometry
  • genetic linkage/association analysis
Selected Publications

Hasan M, Koch J, Rakheja D, Pattnaik AK, Brugarolas J, Dozmorov I, Levine B, Wakeland EK, Lee-Kirsch MA, Yan N
Trex1 regulates lysosomal biogenesis and interferon-independent activation of antiviral genes.
Nat Immunol (Epub 2012 Nov 18) www.ncbi.nlm.nih.gov/pubmed/23160154

Yan N, Regalado-Magdos AD, Stiggelbout B, Lee-Kirsch MA, Lieberman J
The cytosolic exonuclease TREX1 inhibits the innate immune response to HIV-1.
Nat Immunol (Epub 2010 Sept 26) (2010)

Ramantani G, Kohlhase J, Hertzberg C, Innes AM, Engel K, Hunger S, Borozdin W, Mah JK, Ungerath K, Walkenhorst H, Richardt HH, Buckard J, Bevot A, Siegel C, von Stülpnagel C, Ikonomidou C, Thomas K, Proud V, Niemann F, Wieczorek D, Häusler M, Niggemann P, Baltaci V, Conrad K, Lebon P, Lee-Kirsch MA
Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutières syndrome.
Arthritis Rheumat 62: 1469–77 (2010)

Lee-Kirsch MA, Gong M, Chowdhury D, Senenko L, Engel K, Lee Y, De Silva U, Bailey S, Witte T, Vyse TJ, Kere J, Pfeiffer S, Harvey S, Wong A, Koskenmies S, Hummel O, Rohde K, Schmidt RE, Dominiczak AF, Gahr M, Hollis T, Perrino FW, Lieberman J, Hubner N
Mutations in the 3´-5´ DNA exonuclease TREX1 are associated with systemic lupus erythematosus.
Nat Genet 39: 1065–1067 (2007)

Lee-Kirsch MA, Chowdhury D, Harvey S, Gong M, Senenko L, Engel K, Pfeiffer C, Hollis T, Gahr M, Perrino FW, Lieberman J, Hubner N
A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus.
J Mol Med 85: 531–537 (2007)

Lee-Kirsch MA, M. Gong, H. Schulz, F. Ruschendorf, A. Stein, C. Pfeiffer, A. Ballarini, M. Gahr, N. Hubner, and M. Linne
Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps to chromosome 3p.
Am J Hum Genet 79: 731–737 (2006)

CV

since 2012
Professor for Molecular Pediatrics, Medical Faculty, TU Dresden

since 2010
Leader, DFG Clinical Research Unit 249

2008
Habilitation, Medical Faculty, TU Dresden

since 2002
Group leader, Clinical Research, Children’s Hospital, TU Dresden

since 1998
Physician scientist, Children’s Hospital, TU Dresden

1996–1998
Postdoctoral Fellowship, Children’s Hospital and Brigham and Women’s Hospital, Harvard Medical School, Boston

1996
Doctorate degree (Dr. med.), Free University Berlin

Contact

University Hospital Carl Gustav Carus
Technische Universität Dresden
Fetscherstraße 74
01307 Dresden

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